Upfront and interval debulking surgery in advanced/metastatic endometrial cancer in the era of molecular classification
To evaluate oncologic outcomes and prognostic factors of the different molecular subtypes of advanced/metastatic endometrial cancer treated with primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). We conducted a retrospective analysis of patients with endometrial cancer and peritoneal carcinomatosis and/or "bulky" nodal metastasis surgically treated between September 2010 and February 2024. Survival outcomes were compared across four molecular subtypes (p53-mutant, MMR-deficient, NSMP, and POLE-mutant) and surgical approaches. Overall, 51 patients with stage IIIC-IVB endometrial cancer underwent surgical treatment. Thirty-six (70.5 %) patients had PDS followed by adjuvant chemotherapy, while fifteen (29.5 %) received NACT followed by IDS. Most patients in both groups had FIGO stage IVB disease: 24 (66.6 %) in the PDS group and 14 (93.3 %) in the IDS group. Complete cytoreduction was achieved in 83.3 % of the PDS group and 40 % of the IDS group, with no significant differences in postoperative morbidity between the groups. Molecular profiling data were available for most patients, with p53-mutated tumors being the most common subtype (36.1 % in the PDS group and 46.6 % in the IDS group), followed by MMR-deficient tumors (30.5 % in the PDS group and 26.6 % in the IDS group). The type of surgical approach (PDS vs. IDS) did not show a statistically significant correlation with disease-free survival (p = 0.523, log-rank test) or overall survival (p = 0.123, log-rank test). Similarly, molecular classification did not predict patient outcomes in terms of disease-free survival (p = 0.397, log-rank test) or overall survival (p = 0.797, log-rank test). Oncologic outcomes for patients with advanced endometrial cancer remain poor. Neoadjuvant chemotherapy continues to be a viable treatment option for patients with unresectable disease. A personalized approach to neoadjuvant therapy, taking into account histologic and molecular profiles, may improve survival outcomes in this patient population.